Expression of IER3 in hepatocellular carcinoma: clinicopathology, prognosis, and potential regulatory pathways

Abstract

Background Immediate early response 3 (IER3) is correlated to the prognosis of several cancers, but the precise mechanisms underlying the regulation by IER3 of the occurrence and development of hepatocellular carcinoma (HCC) remain unknown. Methods The expression level of IER3 was examined by using in-house immunohistochemistry (IHC), public gene chip, and public RNA-sequencing (RNA-seq). The standardized mean difference (SMD) was calculated to compare the expression levels of IER3 between HCC patients and controls. The summary receiver operating characteristics (sROC) was plotted to comprehensively understand the discriminatory capability of IER3 between HCC and non-HCC group. The Kaplan–Meier curves and the combined hazard ratios (HRs) were used to determine the prognostic value of IER3 in HCC. Moreover, differentially expressed genes (DEGs) and co-expression genes (CEGs) were used to explored the molecular mechanisms of IER3 underlying HCC. hTFtarget was used to predict the transcription factors (TFs) of IER3. The binding site of TFs and the IER3 promoter region was forecasted using the JASPAR website. The relevant ChIP-seq data were used to determine whether TF peaks were present in the IER3 transcription initiation. Results A significantly increased expression of IER3 protein was found in HCC tissue relative to non-HCC tissue as detected by IHC (p < 0.001). Compared to 1,263 cases of non-HCC tissues, IER3 in 1483 cases of HCC tissues was upregulated (SMD = 0.42, 95% confidence interval [CI] [0.09–0.76]). The sROC showed that IER3 had a certain ability at differentiating HCC tissues (area under the curve (AUC) = 0.65, 95% CI [0.61–0.69]). Comprehensive analysis of the effect of IER3 on the prognosis of patients with HCC demonstrated that higher IER3 expression was associated with poor prognosis in HCC (HRs = 1.30, 95% CI [1.03–1.64]). Pathway enrichment analysis revealed that IER3-related genes were mostly enriched in the PI3K-Akt signaling pathway, cancer-related signaling pathways, the p53 signaling pathway, and other signaling pathways. Regulatory factor X5 (RFX5) was identified as a possible regulator of IER3-related TF. Conclusion IER3 may be a potential prognostic marker for HCC. The molecular mechanisms of IER3 in HCC warrant further study.

A comprehensive bioinformatics analysis to identify potential prognostic biomarkers among TNFSF superfamily in breast cancer

“…STAT4 is one of the members of this family, which is very important for promoting immune responses by activating the Janus kinase (JAK)-STAT pathway(95). But according to the studies conducted by Rongquan He, the expression of STAT4 in breast cancer is much higher than in healthy tissue, and with the progress of cancer, the expression of STAT4 also increases, which indicates that this protein may play an important role in the development of breast cancer(96). In addition, it is possible to suppress the proliferation and invasion of cancer cells in colon cancer by silencing the STAT4 gene(97).…”

Explore the impact of hypoxia-related genes (HRGs) in Cutaneous melanoma

“…Indeed, common HRGs, FBP1, GPI, BGN, PKP1, and NDRG1, have been reported as risk factors in CM [ 23 – 27 ] and are associated with immune cell infiltration in the TME. IER3 is a potential prognostic factor in patients with hepatocellular carcinoma and acute myeloid leukemia [ 28 , 29 ]. B4GALNT2 is down-regulated in colorectal and gastric cancers and elevated in breast cancer [ 30 ], and in CM, we report for the first time that it may act as a risk factor influencing patient prognosis.…”